‘Blueprint’ vaccines: the next-generation in the fight against emerging infections

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In the 1790s, smallpox infection was a serious threat to public health. Many died, and those who survived were frequently disfigured with body-covering scars. As the public threat grew, doctors experimented with transferring scab material from a person with a mild case of smallpox into a scratch on a healthy person’s skin. However, people still sometimes died when re-exposed to smallpox.

Then, physician Edward Jenner made a breakthrough. He discovered that a genetic cousin of smallpox, the weaker cowpox, would trigger the body’s immune system to be on alert. When later Jenner introduced the more dire smallpox virus into a cowpox victim, the same patient’s immune system -- having see­­n its close relative before -- was ready. The cowpox vaccine allowed the boy's immune system to identify the smallpox intruder much more quickly, and he was protected from the disease. With this discovery, Jenner jumpstarted the field of immunology and prompted our modern-day understanding of vaccines.

Traditional vaccines, like Jenner’s discovery, deliver protein building blocks from a pathogen into your body, a sort of ‘first look’ at the intruder. This is similar to receiving critical intelligence about an enemy’s plan of attack before the battle starts. Armed with this information, the immune system can mount a specific and robust defense ahead of an actual infection. These protein building blocks are called antigens, unique identifiers of a virus -- much like your fingerprints identify you. Once an immune cell has seen a pathogenic antigen, this information stays on file. When the antigen is encountered again later, the immune cells access their antigenic databases, much like pulling up a fingerprint in CODIS. This critical intelligence informs the immune cells what kind of pathogen they’re dealing with, allowing them to direct the appropriate resources to respond to the threat quickly.

Since Jenner’s breakthrough, advances in vaccine technology in the last century have circumvented many major public health concerns. Indeed, smallpox infection has been completely eradicated worldwide. In the United States, vaccinations have significantly reduced the incidence of nine once-common diseases including those like measles, mumps and rubella -- for every hundred cases there used to be, now there is only one. Public health experts, including those at the World Health Organization, estimate that vaccinations prevent nearly 6 million deaths globally each year.

While current vaccine strategies have taken us a long way, there are still several hurdles to overcome. Some infections, like influenza or Ebola, cross species into humans and mutate rapidly. These fast, tricky infections have proven difficult, cumbersome, or costly for which to develop vaccine strategies. Novel methods are needed to build vaccines against these kinds of hard-to-fight infections and help patients in time.

The newest vaccine strategy to combat tough diseases takes a novel approach to vaccine design. Instead of delivering antigen building blocks, these new vaccines deliver the instructions, or genetic blueprints, for producing pathogenic antigens. What seems like such a simple change -- swapping a whole 3D-antigen for just the instructions to build one -- could be a game-changer in our battle against life-threatening infectious diseases. (In fact, this strategy is already being employed in the search for a vaccine to combat the current Zika virus epidemic.)

Previously, traditional vaccines delivered a fixed amount of antigen to show the immune system, and these antigen signals were relatively transient. Now, the blueprint vaccine is more stable and sticks around in the cell, generating lots of antigen over a longer period of time. Scientists are also developing blueprint vaccines which can be triggered later with an oral pill. These ‘tunable’ vaccines re-initiate antigen production in waves, which has the potential to create a strong immune response over time and may eliminate the need for booster shots.

Blueprint vaccines also promise other practical benefits. Synthesizing physical antigens in the lab is difficult, costly and time-consuming – sometimes it takes months or years to develop a vaccine. Blueprint vaccines, however, can be ready in less than a week. Plus, recent studies illustrate that multiple blueprints for several pathogens can be packaged into a single shot, which could reduce the number of vaccines we’d need to give going forward. This could impact the number of times parents have to take their children for immunizations, and would also make it easier to distribute shots for vaccine-preventable infections in remote locations around the world.

Altogether, blueprint vaccines are a milestone technology in the fight against infectious diseases: they provide long-term immune cues, can be customized to block multiple pathogens at once, and can be produced quickly. The lower costs associated with developing and disseminating effective blueprint vaccines will be especially important for resource-poor regions of the world. While research is still ongoing to fully develop the potential here, we can expect this new class of vaccines to make a powerful impact in the fight against serious infectious diseases.

Comments

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